The receptor CC-chemokine receptor 7 (CCR7) is known to play an important role in balancing immunity and tolerance, in particular self-tolerance (Förster, Davalos-Misslitz et al. 2008). Its two ligands, CC-chemokine ligand-19 (CCL19) and -21 (CCL21) play an important role in immunity and inflammation. In particular, CCR7 and its ligands seem to play an important role in homing of subpopulations of T cells and antigen-presenting cells like dendritic cells (DCs) to the lymph nodes (LNs). The lymph nodes are implicated as locations for development of both protective immunity to exogenous antigens and tolerance to self-antigens, and in guiding the interactions between such cell types that lead to T cell education.
In the scientific literature, CCL19 and CCL21, along with their receptor CCR7, have been shown to be generally necessary in the establishment of self-tolerance, both in physiological and pathophysiology situations. For example, mice that are deficient in CCR7 are prone to develop generalized multi-organ autoimmunity, characterized by lymphocyte infiltrates in peripheral organs, circulating autoantibodies, and IgG deposition on renal glomeruli (Davalos-Misslitz, Rieckenberg et al. 2007). Furthermore, mice that lack CCR7 ligands, plt mice, show defective migration of naïve T cells and activated dendritic cells to the lymph nodes, show delayed but ultimately enhanced T cell activation as measured by antigen-specific T cell proliferation and cytokine production. These T cell responses were shifted from the lymph node to the spleen (Mori, Nakano et al. 2001). A later study showed prolong expansion of antigen-specific CD4+ T cells in the draining lymph nodes of plt mice compared to wild-type mice after immunization due to activation-induced cell death by CCR7 ligands (Yasuda, Kuwabara et al. 2007), while another study showed that CCR7 signaling inhibits T cell proliferation (Ziegler, Oberbarnscheidt et al. 2007). Together, these data from the literature show CCR7-dependent migration of cells to be required for maintaining tolerance to self-antigens, but redundant for mounting cytotoxic T cell responses.